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Resistance mutations were assessed using the HIV Stanford Database, and the proportion of cases versus controls with PDR to their ART regimens was compared.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>PDR was observed in 7 participants (11.3%; 95% CI 4.7, 21.9) and did not differ between 21 cases and 41 controls (4.8% vs 14.6%, p = 0.4061). PDR detected only as minority variants was less common (3.2%; 95% CI 0.2, 11.7) and also did not differ between groups (0% vs. 4.9%; p = 0.5447). Cases\u2019 median plasma HIV RNA at delivery was 347c\/mL, with most (n = 19\/22) showing progressive diminution of viral load but not \u2264200c\/mL. Among cases with viral rebound (n = 3\/22), none had PDR detected. Virologic non-suppression at term was associated with higher plasma HIV RNA at study entry (p&lt;0.0001), a shorter duration of ART prior to delivery (p&lt;0.0001), and randomization to efavirenz- (versus raltegravir-) based ART (p = 0.0085).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We observed a moderate frequency of PDR that did not significantly contribute to virologic non-suppression at term. Rather, higher pretreatment plasma HIV RNA, randomization to efavirenz-based ART, and shorter duration of ART were associated with non-suppression. These findings support early prenatal care engagement of pregnant women and initiation of integrase inhibitor-based ART due to its association with more rapid suppression of plasma RNA levels. Furthermore, because minority variants appeared infrequent in ART-na\u00efve pregnant women and inconsequential to ART-suppression, testing for minority variants may be unwarranted.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0275254","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T17:28:36Z","timestamp":1664299716000},"page":"e0275254","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of minority frequency pretreatment HIV drug-resistant variants in pregnant women and associations with virologic non-suppression at term"],"prefix":"10.1371","volume":"17","author":[{"given":"Ceejay L.","family":"Boyce","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid A.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila M.","family":"Styrchak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha R.","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson J.","family":"Wallner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross S.","family":"Milne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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Department of Health and Human Services [https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/AdultandAdolescentGL.pdf."},{"key":"pone.0275254.ref010","article-title":"Impact of next generation sequencing defined HIV pre-treatment drug resistance on virological outcomes in the ANRS 12249 treatment as prevention trial","author":"A Derache","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"5","key":"pone.0275254.ref011","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1016\/S2352-3018(20)30038-2","article-title":"Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial","volume":"7","author":"EC Joao","year":"2020","journal-title":"Lancet HIV"},{"issue":"12","key":"pone.0275254.ref012","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/infdis\/jix544","article-title":"Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013\u20132014","volume":"216","author":"RA Silverman","year":"2017","journal-title":"J Infect Dis"},{"issue":"5","key":"pone.0275254.ref013","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"H Li","year":"2010","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0275254.ref014","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/nar\/gkg100","article-title":"Human immunodeficiency virus reverse transcriptase and protease sequence database","volume":"31","author":"SY Rhee","year":"2003","journal-title":"Nucleic Acids Res"},{"issue":"Suppl 1","key":"pone.0275254.ref015","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1086\/505356","article-title":"Rationale and uses of a public HIV drug-resistance database","volume":"194","author":"RW Shafer","year":"2006","journal-title":"J Infect Dis"},{"key":"pone.0275254.ref016","unstructured":"HIV Drug Resistance Report 2019. 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Rahangdale","year":"2016","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"pone.0275254.ref023","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1089\/apc.2012.0283","article-title":"Rapid decline in HIV viral load when introducing raltegravir-containing antiretroviral treatment late in pregnancy","volume":"26","author":"K Westling","year":"2012","journal-title":"AIDS Patient Care STDS"},{"issue":"4","key":"pone.0275254.ref024","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1086\/318530","article-title":"Perinatal Transmission of Human Immunodeficiency Virus Type 1 by Pregnant Women with RNA Virus Loads <1000 Copies\/mL","volume":"183","author":"JPA Ioannidis","year":"2001","journal-title":"The Journal of Infectious Diseases"},{"issue":"2","key":"pone.0275254.ref025","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/hiv.12397","article-title":"HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa","volume":"18","author":"L Myer","year":"2017","journal-title":"HIV Med"},{"issue":"5","key":"pone.0275254.ref026","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.1016\/S2352-3018(20)30050-3","article-title":"Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial","volume":"7","author":"K Kintu","year":"2020","journal-title":"Lancet HIV"},{"issue":"10281","key":"pone.0275254.ref027","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(21)00314-7","article-title":"Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010\/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial","volume":"397","author":"S Lockman","year":"2021","journal-title":"Lancet"},{"issue":"7","key":"pone.0275254.ref028","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/cid\/ciz372","article-title":"Clinical Impact and Cost-effectiveness of Genotype Testing at Human Immunodeficiency Virus Diagnosis in the United States","volume":"70","author":"EP Hyle","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"9","key":"pone.0275254.ref029","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1056\/NEJMoa1902824","article-title":"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV","volume":"381","author":"WDF Venter","year":"2019","journal-title":"N Engl J Med"},{"issue":"9","key":"pone.0275254.ref030","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1056\/NEJMoa1904340","article-title":"Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1","volume":"381","author":"NAS Group","year":"2019","journal-title":"N Engl J Med"},{"issue":"7","key":"pone.0275254.ref031","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1093\/jac\/dky093","article-title":"Dolutegravir-based maintenance monotherapy versus dual therapy with lamivudine: a planned 24 week analysis of the DOLAM randomized clinical trial","volume":"73","author":"JL Blanco","year":"2018","journal-title":"J Antimicrob Chemother"},{"issue":"9","key":"pone.0275254.ref032","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1093\/cid\/ciy1132","article-title":"Dolutegravir Monotherapy Versus Dolutegravir\/Abacavir\/Lamivudine for Virologically Suppressed People Living With Chronic Human Immunodeficiency Virus Infection: The Randomized Noninferiority MONotherapy of TiviCAY Trial","volume":"69","author":"L Hocqueloux","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"12","key":"pone.0275254.ref033","doi-asserted-by":"crossref","first-page":"e547","DOI":"10.1016\/S2352-3018(17)30152-2","article-title":"Dolutegravir as 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